Abstract
We describe the details of the magnetic resonance spectroscopy and chemical shift imaging techniques for the human brain which have been developed over the last two decades. With these non-invasive tools, it is now readily possible to repeatedly assay up to 20 common brain metabolites. From the perspective of drug discovery, each of these metabolites could fulfill a number of useful functions: disease biomarker, surrogate marker of drug delivery, surrogate marker of drug efficacy and so on. To facilitate the possible utility of clinical magnetic resonance spectroscopy in future drug discovery, the major portion of the review is devoted to a detailed description of the well-validated neurochemical profiles of many common human brain disorders, for which MRS data now exists. Beyond proton, MRS, the commonest tool provided by the manufacturers of clinical MRI equipment, lays the world of heteronuclear NMR more familiar to chemists. Here too, with relatively little effort it has been possible to define neurochemical profiles of human brain disorders using 13C MRS. The future for drug discovery scientists is discussed. Finally, recognizing that a known feature of MR is the lack of sensitivity, we describe new efforts to harness hyperpolarization, with its 50,000 signal amplification, to conventional MRS.
Keywords: Spectroscopy, metabolites, biomarkers, drug discovery, MR spectroscopy, MRS, molecular imaging, Positron Emission Tomography, PET, neurospectroscopy, ISIS, PRESS, STEAM, CSI, nuclear Overhauser effect, NOE, N-Acetylaspartate, NAA, Creatine, Phosphocreatine, Myo-Inositol, Scyllo-Inositol, astrocytes, pseudodementia, Hepatic encephalopathy, transient ischemic attack (TIA), MELAS, mitochondrial encephalopathy with lactic acidosis, Neonatal hypoxia, Closed Head Trauma, Closed head injury, traumatic brain injury, Toxoplasmosis, CNS lymphoma, progressive multifocal leukoencephalopathy, Cryptococcoma, cytochrome P4502D6, CYP2D6, P-glycoprotein efflux transport, receptor imaging indicators
Current Topics in Medicinal Chemistry
Title: Application of NMR Spectroscopy in Medicinal Chemistry and Drug Discovery
Volume: 11 Issue: 1
Author(s): Brian Ross, Thao Tran, Pratip Bhattacharya, D. Martin Watterson and Napapon Sailasuta
Affiliation:
Keywords: Spectroscopy, metabolites, biomarkers, drug discovery, MR spectroscopy, MRS, molecular imaging, Positron Emission Tomography, PET, neurospectroscopy, ISIS, PRESS, STEAM, CSI, nuclear Overhauser effect, NOE, N-Acetylaspartate, NAA, Creatine, Phosphocreatine, Myo-Inositol, Scyllo-Inositol, astrocytes, pseudodementia, Hepatic encephalopathy, transient ischemic attack (TIA), MELAS, mitochondrial encephalopathy with lactic acidosis, Neonatal hypoxia, Closed Head Trauma, Closed head injury, traumatic brain injury, Toxoplasmosis, CNS lymphoma, progressive multifocal leukoencephalopathy, Cryptococcoma, cytochrome P4502D6, CYP2D6, P-glycoprotein efflux transport, receptor imaging indicators
Abstract: We describe the details of the magnetic resonance spectroscopy and chemical shift imaging techniques for the human brain which have been developed over the last two decades. With these non-invasive tools, it is now readily possible to repeatedly assay up to 20 common brain metabolites. From the perspective of drug discovery, each of these metabolites could fulfill a number of useful functions: disease biomarker, surrogate marker of drug delivery, surrogate marker of drug efficacy and so on. To facilitate the possible utility of clinical magnetic resonance spectroscopy in future drug discovery, the major portion of the review is devoted to a detailed description of the well-validated neurochemical profiles of many common human brain disorders, for which MRS data now exists. Beyond proton, MRS, the commonest tool provided by the manufacturers of clinical MRI equipment, lays the world of heteronuclear NMR more familiar to chemists. Here too, with relatively little effort it has been possible to define neurochemical profiles of human brain disorders using 13C MRS. The future for drug discovery scientists is discussed. Finally, recognizing that a known feature of MR is the lack of sensitivity, we describe new efforts to harness hyperpolarization, with its 50,000 signal amplification, to conventional MRS.
Export Options
About this article
Cite this article as:
Ross Brian, Tran Thao, Bhattacharya Pratip, Martin Watterson D. and Sailasuta Napapon, Application of NMR Spectroscopy in Medicinal Chemistry and Drug Discovery, Current Topics in Medicinal Chemistry 2011; 11 (1) . https://dx.doi.org/10.2174/156802611793611850
DOI https://dx.doi.org/10.2174/156802611793611850 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Pharmacological Potential of Exercise and RAS Vasoactive Peptides for Prevention of Diseases
Current Protein & Peptide Science Historical Aspects and Relevance of the Human Coronary Collateral Circulation
Current Cardiology Reviews Role of Cardiac Magnetic Resonance Imaging in Patients with Idiopathic Ventricular Arrhythmias
Current Cardiology Reviews Insights into the Role of Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases in Health and Disease
Current Chemical Biology Atrial Fibrillation and Hypertension: “Quo Vadis”
Current Hypertension Reviews Ultrasound Techniques for Drug Delivery in Cardiovascular Medicine
Current Drug Discovery Technologies TSH Variations in Chronic Heart Failure Outpatients: Clinical Correlates and Outcomes
Endocrine, Metabolic & Immune Disorders - Drug Targets Health Benefits of Honey: Implications for Treating Cardiovascular Diseases
Current Nutrition & Food Science Red Cell Glycolytic Enzyme Disorders Caused by Mutations: An Update
Cardiovascular & Hematological Disorders-Drug Targets Gender Differences in Ischemic Heart Disease
Recent Patents on Cardiovascular Drug Discovery Heat Shock Protein-60 and Risk for Cardiovascular Disease
Current Pharmaceutical Design Mitochondrial MMP Activation, Dysfunction and Arrhythmogenesis in Hyperhomocysteinemia
Current Vascular Pharmacology Periostin as a Heterofunctional Regulator of Cardiac Development and Disease
Current Genomics Mitochondrial Injury and Targeted Intervention in Septic Cardiomyopathy
Current Pharmaceutical Design Ablation of Complex Fractionated Atrial Electrograms in Catheter Ablation for AF; Where have we been and where are we going?
Current Cardiology Reviews Targeted Therapies in Solid Tumours: Pinpointing the Tumours Achilles Heel
Current Pharmaceutical Design Editorial [Hot Topic: Why Apoptosis in Pediatric Disorders?]
Current Pediatric Reviews Population Pharmacogenomics and Personalized Medicine Research in Hungary: Achievements and Lessons Learned
Current Pharmacogenomics and Personalized Medicine Apelin in the Control of Body Fluid Homeostasis and Cardiovascular Functions
Current Pharmaceutical Design Beyond Ejection Fraction: Novel Clinical Approaches Towards Sudden Cardiac Death Risk Stratification in Patients with Dilated Cardiomyopathy
Current Cardiology Reviews